Having died of snakebit, cholera, measles, drowning, and--yes--dystentery many, many times, I quite naturally have an interest in a subset of your question: how dangerous was the Oregon Trail, for real? Although there will never be a definitive answer thanks to the nature of the sources, John Unruh's examination of the question in The Plains Across is generally treated as authoritative today. (And the book remains the most solid and exhaustive study of the Oregon Trail, although it's not nearly as fun reading as individual diaries.)

Piecing together direct mentions and overheard rumors in travel diaries, along with trailside grave markers, Unruh considers that there are two basic questions to consider: how many people died, and how they died. He notes that by far the most people who died, died of disease, and that travelers on the Oregon Trail were just as susceptible to bad years of epidemic (especially cholera) as people "back east." This is a crucial observation for considering how dangerous pioneering was in and of itself--the biggest killers on the Trail were basically the same risks a person would run back home.

Emphasizing that we can't extrapolate from the mortality rate of bad cholera years to every year, Unruh falls on the more conservative side of the 3-10% range into which basically every estimate has fallen. He thinks around a 4% mortality rate, which is the generally accepted number.

But Unruh has one further MAJOR myth to dispel (although in my own recollection, it's less present in the video game than if you drive west and stop at all the historic markers). Even though the mortality rate for traveling to Oregon versus staying back east was basically a wash, there were a few Trail-specific or Trail-increased risks to take. The biggest one he finds, by far, was drowning. Wagon-related fatal injuries were another pioneer-focused cause of death. Women's diaries, in particular, recount tragic stories of children crushed to death under relentless wagon wheels.

What Unruh finds very very little trace of, which was apparently a revolutionary argument in 1979, is pioneer deaths from attacks by Native Americans. James Loewen's book Lies Across America, which critiques the accuracy of U.S. National Historic Sites (some museum-type sites, but a lot more of the "roadside marker" type), draws this out in horrifying detail--just how many "massacres by Indians" either didn't happen or were pioneer massacres of local Native Americans. Unruh's conclusion here, in conjunction with his recognition that not every year was an epidemic year, is the major reason he concludes the lower mortality rate is correct (and why modern scholars accept his take over the earlier, mostly higher ones).

I've only done research on the Oregon Trail part of the question, for reasons that have become obvious throughout the post. However, I would posit that Unruh's point about comparative mortality rate holds fairly true. Most premature deaths were probably a wash 'back home' or 'out there', coming from similar causes. The increased deaths from pioneering causes were probably balanced out by the higher disease rates in more populated areas--until the mid-ish 19th century, mortality rates in cities were higher/life expectancy was lower thanks to disease and worse sanitation (they tried; they just weren't so successful).

Sorry for the delayed reply!